福島医学雑誌 60 巻 4 号　2010

〔症例報告〕

分子標的治療薬Bevacizumab治療中に腸管穿孔を来たした再発卵巣癌症例

矢澤　浩之¹⁾，遠藤　澄子¹⁾，林　章太郎¹⁾，大石　明雄2)，山田　秀和³⁾，藤森　敬也³⁾

¹⁾福島赤十字病院産婦人科，²⁾同　外科，³⁾福島県立医科大学産科婦人科

（受付2010年6月11日　受理2010年10月7日）

A Case of Bowel Perforation in a Patient with Advanced Recurrent Ovarian Cancer Treated with the Molecular Targeted Agent Bevacizumab

HIROYUKI YAZAWA¹⁾, SUMIKO ENDO¹⁾, SHOUTARO HAYASHI¹⁾, AKIO OISHI²⁾, HIDEKAZU YAMADA³） and KEIYA FUJIMORI^3）

¹⁾Department of Obstetrics and Gynecology, ²⁾Department of Surgery, Fukushima Red Cross Hospital, 960-8530, Japan and ³⁾Department of Obstetrics and Gynecology, Fukushima Medical University, 960-1295, Japan

要旨: 症例は60歳。腹部膨満感，食欲不振を主訴に前医を受診し，腹腔内腫瘤を認めたため卵巣腫瘍が疑われ当科へ紹介となった。CT, MRI検査にて骨盤腔内に直径10cmを超える充実性で一部嚢胞性の腫瘍と傍大動脈リンパ節の著明な腫大を認めた。CA125は976.5U/mlと著明に上昇しており卵巣癌を疑い手術を行った。腫瘍は小腸へ浸潤しており腸管部分切除，子宮全摘，付属器摘出，骨盤リンパ節郭清術を行った（suboptimal surgery）。組織はendometrioid adenocarcinomaであった。術後TC療法（PTX;175mg/m²+CBDCA;AUC, 5）にて傍大動脈リンパ節の残存腫瘍は消失，CA125も正常値となり緩解状態を維持していたが，手術から2年後に再発を認めた。Second line（CPT-11）は副作用のため続行困難，third line（docetaxl+gemcitabin）は効果なく，fourth lineとしてbevacizumab（10mg/kg，2週毎i.v.）+cycloposphamide（50mg連日内服）による分子標的治療を選択した。治療によりCA125は下降し，再発腫瘍の縮小効果（縮小率40%）を認めたが4コース終了時に小腸穿孔を起こした。穿孔は腟断端との間に小腸腟瘻を形成していたが，開腹のうえ小腸部分切除，膣断端縫合を行い修復し得た。術後にはsalvage chemotherapyとして経口etoposide （50mg/day)，TC療法等を行い1年以上経過するがstable diseaseの状態を維持している。消化管穿孔は生命を脅かす重篤な合併症であり，穿孔発症に関わる因子（リスク因子）を詳細に解明し，その発症を予防することが重要となる。

索引用語: 再発卵巣癌，化学療法，bevacizumab，分子標的治療，消化管穿孔

Abstract: A 60-year-old woman presented with abdominal distension and appetite loss. CT scan and MRI revealed the presence of a solid tumor over 10cm in diameter in the pelvic cavity, and serum CA125 was remarkably elevated (976.5U/ml). Ovarian carcinoma was highly suspected and surgery was performed. Two sites of carcinoma invasions into the intestinal wall were recognized, and partial resection of the small intestine was performed with hysterectomy, adnectomy and pelvic lymphadnectomy (suboptimal surgery). Histological findings suggested endometrioid adenocarcinoma. Post operatively, TC chemotherapies (PTX;175mg/m²+CBDCA;AUC, 5) were performed and the residual tumors of paraaortic region disappeared after several cycles of treatments. Although the remission was achieved and sustained, the tumor recurrence was recognized after 2 years after the first operation. After second- and third-line chemotherapies, treatments using the molecular targeted agent bevacizumab were performed as a fourth-line therapy (bevacizumab, 10mg/kg, every 2weeks, i.v.+cycloposphamide, 50mg/day, p.o.). With the treatments, although the recurrent paraaortic tumor size reduced 40%, intestinal perforation occurred after 4 cycles of the regimen. The perforation formed a fistula between the ileum and vaginal stump therefore necessitating repair by partial ileotomy. Salvage chemotherapies using oral etoposide or weekly TC chemotherapies were continued after the second operation and the patient is presently alive with stable disease over 1 year after her perforation. Gastrointestinal perforation is a catastrophic complication that is associated with a high rate of patient mortality, therefore, it is very important to evaluate the risk factors before chemotherapy to prevent its occurrence.

Key words: recurrent ovarian cancer, chemotherapy, bevacizumab, molecular targeted therapy, gastrointestinal perforation